A novel spray-drying process is disclosed. The process can lead to spray-dried products with improved properties, as well as increased throughput relative to conventional spray-drying processes.
The use of spray drying to produce powders from fluid feed stocks is well known, with applications ranging from powdered milk to bulk chemicals and pharmaceuticals. See U.S. Pat. No. 4,187,617 and Mujumbar et al., Drying 91, pages 56-73 (1991). See also Masters, Spray Drying Handbook, pages 263-268 (4th edition, 1985). The use of spray drying to form solid amorphous dispersions of drugs or active agents and concentration-enhancing polymers is also known. See commonly owned U.S. Pat. Nos. 6,763,607 and 6,973,741.
When it is desired to form a spray-dried product in which the drug or active agent is amorphous, it is desirable to have the active agent fully dissolved in the spray solution when it is atomized into droplets. Specifically, when it is desired to form a spray-dried product in which the amorphous active agent is dispersed in one or more other materials, termed matrix material, it is generally desired to have at least a part and often all of the matrix material also dissolved in the spray solution. In such cases, the throughput of a conventional spray-drying process is often limited by the amount of active agent and matrix material that can be dissolved in the spray solution. It is generally known that the solubility of many substances, such as active agents and matrix materials, often increases as the temperature of the solvent is increased. However, industry avoids using elevated temperatures when using organic solvents, due to the inherent dangers and safety concerns when processing organic solvents, which are often flammable at high temperatures. In addition, conventional spray-drying processes avoid use of elevated temperatures out of concern for the thermal stability of the active agent and matrix material-degradation of the active agent and/or the matrix material can lead to unwanted breakdown products in the particles produced.
Because of this, conventional spray-drying solutions are generally kept at or near room temperature when entering the spray nozzle. This limits the throughput of the process due to the often low solubility of active agents and matrix materials in the solvents used. In addition, when the solubility of the active agent in the spray solution is low, the active agent is often dissolved to near its solubility limit to achieve as high a throughput as possible. The spray-dried products obtained from such solutions are often not homogeneous. Finally, conventional spray-dried processes often produce products that suffer from not being homogeneous because the rate of solvent removal is not sufficiently fast, and broad ranges of particle sizes are produced because the atomization means produces a wide range of droplet sizes.
U.S. Patent Application Publication No. 2008/0248114A1 describes the production of solid solutions containing poorly-soluble active substances using a spray-drying process utilizing short-term heating and rapid drying. The process avoids organic solvents by utilizing a feed stream that is an aqueous suspension of the active. The aqueous suspension is heated to allow dissolution of the active in the spray solution. However, this process is limited to actives that have a high solubility in water at elevated temperature.
What is needed is a spray-drying process that results in improved properties of the spray-dried product, such as a higher degree of homogeneity and more uniform particle size, and that improves the throughput of spray-drying equipment while spraying solutions of an active agent and the matrix material, and provides a safe, reproducible process to produce high-quality product. Such a process promises to increase the quality and decrease manufacturing costs for spray-dried products.